LOXL3 Function Beyond Amino Oxidase and Role in Pathologies, Including Cancer

Abstract

Lysyl oxidase like 3 (LOXL3) is a copper-dependent amine oxidase responsible for the crosslinking of collagen and elastin in the extracellular matrix. LOXL3 belongs to a family including other members: LOX, LOXL1, LOXL2, and LOXL4. Autosomal recessive mutations are rare and described in patients with Stickler syndrome, early-onset myopia and non-syndromic cleft palate. Along with an essential function in embryonic development, multiple biological functions have been attributed to LOXL3 in various pathologies related to amino oxidase activity. Additionally, various novel roles have been described for LOXL3, such as the oxidation of fibronectin in myotendinous junction formation, and of deacetylation and deacetylimination activities of STAT3 to control of inflammatory response. In tumors, three distinct roles were described: (1) LOXL3 interacts with SNAIL and contributes to proliferation and metastasis by inducing epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells; (2) LOXL3 is localized predominantly in the nucleus associated with invasion and poor gastric cancer prognosis; (3) LOXL3 interacts with proteins involved in DNA stability and mitosis completion, contributing to melanoma progression and sustained proliferation. Here we review the structure, function and activity of LOXL3 in normal and pathological conditions and discuss the potential of LOXL3 as a therapeutic target in various diseases.

Roles of Lysyl Oxidase Family Members in the Tumor Microenvironment and Progression of Liver Cancer

“…Similarly, while the role of LOXL3 in gastric cancer [ 38 ], colorectal cancer [ 39 ], PDAC [ 40 ], and ovarian cancer [ 41 ] has been reported, its significance in liver cancer awaits further investigation.…”

Transcriptional profiling of embryo cryotolerance

“…The overexpressed HC genes FREM1, ZNF135, LOXL3, and CLDN8 are related to cellular organization and structure (Bai et al, 2011;Laurentino et al, 2019;Nishioka et al, 2012;Smyth et al, 2004;Watson et al, 2004) (Nishioka et al, 2012). Interestingly, LOXL3 possesses a potential transcription factor binding site for STAT3, which is fundamental for embryonic growth (Laurentino et al, 2019). Additionally, the gene CLDN8, a crucial constituent of tight junction complexes, regulates paracellular transport (the movement of water and solutes between epithelial and endothelial cell sheets) and the maintenance of polarity of epithelial cells (Watson et al, 2004).…”

The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ‐related proteins and identification of protein domain families

“…Accordingly, the Pfam matches of the Bark beetle (Anakonda) protein were included in the SRCR family, the members of which are believed to participate in versatile functions, including epithelial homeostasis and modulation of the immune response 130 . Interestingly, the SRCR domain of Loxl3 has been demonstrated to show deacetylase/deacetyliminase activity thus contributing to STAT3 deacetylation and controlling inflammatory responses 131,132 …”